How the immune system works

What you'll learn: what the immune system is for, which parts it is made of, and how its two main branches share the work of fighting an infection.

This course is general education about how the body works, not medical advice. If you are unwell or have questions about your own health, vaccines or treatment, talk to a doctor, nurse or pharmacist.

Meet Tom, and his flu

Tom is 38 and drives a city bus. One Tuesday in January a passenger coughs near the front of the bus, and a few tiny droplets carrying influenza virus land in Tom's nose. He doesn't notice. Two days later he has a fever, aching muscles and a dry cough. About a week after that he is back at work, a little tired but recovered, and his body now carries a lasting record of that exact virus.

This course follows that one infection, step by step, from the first virus particle to the memory it leaves behind. Each lesson picks up Tom's flu where the last one left it, so by the end you will be able to explain what happened inside him on every day of it.

What the immune system is for

Your body is warm, wet and full of nutrients, which makes it an excellent home for microbes. Most of the microbes you meet are harmless, and many that live on your skin and in your gut are useful. A small number cause disease: these are called pathogens. They come in four broad kinds:

• Viruses, like influenza, which can only multiply inside your own cells.
• Bacteria, single cells that can live outside your cells, such as the ones that infect a dirty cut.
• Fungi, such as the yeasts behind thrush.
• Parasites, from single-celled ones like the malaria parasite to worms.

The immune system's job is to keep pathogens out, find the ones that get in, destroy them, and clear up afterwards, all without wrecking your own healthy tissue. That last part is just as important as the first. Many of the problems we will meet later in the course, such as allergies and autoimmune disease, are cases of the immune system aiming at the wrong target.

Where it lives

Unlike the heart or the liver, the immune system is not one organ. It is a network of cells, proteins and tissues spread through the whole body.

White blood cells are the immune system's workforce. There are several families of them, and you will meet each one as Tom's flu progresses.

Two branches: fast and general, slow and precise

Immunologists divide the system into two branches that work together.

Innate immunity is the part you are born with. It responds within minutes to hours, and it recognises broad patterns that many microbes share, such as types of genetic material or bacterial cell walls that human cells never make. It includes the barriers of skin and mucus, cells that swallow invaders, and signalling molecules that raise the alarm. It reacts the same way every time.

Adaptive immunity is slower to start, taking around a week or two the first time it meets a new pathogen. In exchange it is extraordinarily precise. Its cells, called B cells and T cells, each carry receptors that recognise one specific molecular shape. Out of millions of different cells, the few that match the invader are selected and multiplied. Crucially, adaptive immunity remembers: the next time the same pathogen turns up, the response is faster and stronger.

Think of a town with a night watch and a team of detectives. The night watch patrols every street, recognises trouble in general terms ("someone is breaking a window") and acts immediately. The detectives take days to build a case, but once they have identified the specific culprit, they can track down that one person anywhere, and they keep the file afterwards. The night watch also matters to the detectives: it is the watch that brings in the evidence. In the body, innate cells carry pieces of the invader to the adaptive cells, which is how the slow, precise response gets started.

Tom's infection on a timeline

Here is the outline of what will happen inside Tom. Each step is a lesson later in the course.

1. Day 0: virus lands in his nose and meets mucus, the first barrier.
2. Hours to day 1: some virus gets into the cells lining his airways and starts to multiply; infected cells sound an alarm.
3. Days 1 to 3: innate cells pour in, inflammation and fever begin, and Tom feels ill.
4. Days 2 to 5: cells carrying pieces of virus reach his lymph nodes and activate matching T and B cells.
5. Days 5 to 10: antibodies and killer T cells clear the infection.
6. Weeks to years: memory cells stay behind, ready for next time.

These timings are typical rather than exact. They vary from person to person and between strains of flu.

Recap

• Pathogens are the minority of microbes that cause disease: viruses, bacteria, fungi and parasites.
• The immune system is a body-wide network, not one organ, with white blood cells as its workforce.
• Innate immunity is fast and general; adaptive immunity is slow at first, precise, and has memory.
• The two branches depend on each other: innate cells bring the evidence that starts the adaptive response.
• Tom's flu, from a cough on his bus to lasting memory, is the case we will follow through every lesson.

What you'll learn: how skin, mucus, acids and friendly microbes stop most pathogens before any immune cell has to act, and how Tom's flu virus got past them.

The defence you never notice

The droplets from the passenger's cough landed on the inside of Tom's nose. Before any white blood cell gets involved, a virus has to get through a set of physical and chemical barriers. They work so well, and so quietly, that most of the microbes you breathe in, eat or touch every day never get a foothold. When an infection does happen, it is usually because a pathogen has found a way through, round or past these defences.

Skin: a wall of dead cells

Your skin's outer layer is made of flattened, dead cells packed with a tough protein called keratin. They are stacked like overlapping roof tiles and constantly shed, taking any microbes on them along. Very few pathogens can cross intact skin, which is why most infections start where skin is broken (a cut or a burn) or where it is replaced by thinner linings (the nose, mouth, eyes, gut and genitals).

Skin also fights chemically. Its surface is mildly acidic, which discourages many bacteria. Sweat and the oils from sebaceous glands contain fatty acids and small antimicrobial proteins. And skin is covered in harmless resident bacteria that occupy the space and nutrients a pathogen would need.

Mucus and the airway's conveyor belt

Tom's virus didn't meet skin; it met the lining of his nose and airways. These linings are wet and thin, because they have to let gases and fluids through, so they rely on a different trick.

A layer of sticky mucus covers them. Mucus traps particles, dust and microbes. Beneath it, the lining cells carry tiny hair-like projections called cilia, which beat in coordinated waves and push the mucus steadily upward and outward toward the throat, where it is swallowed or coughed up. Doctors call this the mucociliary escalator, but you can picture it as a conveyor belt: anything that lands on it is carried away before it can settle. Swallowed microbes then meet stomach acid, which kills most of them.

Mucus also contains defensive molecules. For flu, the most interesting are sugar-tipped proteins that look like the receptors flu uses to enter cells. The virus grabs these decoys instead of real cells and is carried off on the belt.

Smoking damages cilia and slows the conveyor belt down, which is one reason smokers get more chest infections. Very dry air may also make mucus less effective, though how much that contributes to winter flu seasons is still being studied.

Chemical defences in fluids

Your body fluids are laced with antimicrobial chemistry:

The last row deserves a word. Your gut alone hosts trillions of bacteria. A course of antibiotics can thin out these residents, and that is one reason some people get a gut infection such as Clostridioides difficile afterwards: the competition that kept it in check has been removed.

How flu gets through

No barrier is perfect. Influenza is good at its job because its surface is studded with a protein called haemagglutinin (spelled hemagglutinin in American English), which latches onto sugar molecules on the surface of airway cells. A second surface protein, neuraminidase, works like a pair of scissors that cuts the virus free from mucus decoys and, later, from the cell it has infected.

In Tom's case, here is what happened in the first few hours:

1. Most droplets landed on mucus and were swept toward his throat and swallowed.
2. Some virus particles were caught by decoy molecules in the mucus.
3. A few used neuraminidase to slip through the mucus layer and reach the cells beneath.
4. Those particles bound to the cells with haemagglutinin, were taken inside, and began to copy themselves.

Within roughly six to eight hours a single infected cell can release many new virus particles, which infect neighbouring cells. Tom still feels perfectly well. The barriers have lost this round, and the next line of defence, the innate alarm system, now has to notice.

Why this matters for everyday life

Barriers explain a lot of ordinary health advice. Handwashing with soap removes microbes before they reach your eyes, nose or mouth. Covering a cough keeps droplets out of the air. Keeping a cut clean helps stop bacteria from getting through a broken skin barrier. None of this is glamorous, but it reduces the number of pathogens your immune cells ever have to deal with.

Recap

• Most pathogens never get past the barriers: skin, mucus, acids, antimicrobial proteins and resident microbes.
• Intact skin is a near-impenetrable wall; most infections start at a break in it or on a thin lining.
• In the airways, sticky mucus and beating cilia act as a conveyor belt that carries trapped microbes away.
• Flu uses haemagglutinin to attach to airway cells and neuraminidase to cut itself free.
• In Tom's nose, a few virus particles got through the mucus and began copying themselves inside his cells.